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Why does cancer arise? Landmark study provides unique insight

A massive research effort that started more than a decade ago has completed a comprehensive PanCancer Atlas that, for the first time, offers researchers and clinicians alike a way to fully understand cancer according to its genomic and molecular features.

Researchers reveal the detail included within the PanCancer Atlas.

The PanCancer Atlas is so vast that it spans more than two dozen scientific papers published in several Cell journals.

This was sponsored by two institutes within the National Institutes of Health (NIH): the National Cancer Institute (NCI) and the National Human Genome Research Institute.

More than 150 researchers at more than two dozen research establishments across the United States have worked on the $300 million program.

"This project," says Dr. Francis S. Collins, the director of the NIH, "is the culmination of more than a decade of groundbreaking work."

You can access the newly published PanCancer Atlas papers through a portal that groups them into three categories: "cell-of-origin patterns, oncogenic processes, and signaling pathways."

Looking at cancer from a different angle

Cancer is a disease that arises when cells start to grow out of control because of errors in their DNA.The traditional way of classifying cancer is according to where it starts in the body — for example, breast cancer, prostate cancer, or stomach cancer.

The work that culminated in the PanCancer Atlas was launched as the Pan-Cancer Initiative at a meeting in 2012 that took place in Santa Cruz, CA.

By then, scientists were already noticing some interesting features about cancer that led them to question the traditional way of classifying the disease.

One interesting feature was that some cancers were similar at the molecular level, despite the fact that they had started in different parts of the body.

Another interesting feature was that cancers that started in the same tissue could be quite different at the molecular level, possessing distinct "genomic profiles."

Implications for researchers and clinicians

These early molecular insights spurred researchers to investigate how changes in each cancer's genome — the complete set of its DNA — might drive the disease.

The PanCancer Atlas is a product of this effort and will pave the way to improving prevention, detection, and treatment of cancer in its various forms.

As Pan-Cancer Initiative co-organizer Josh Stuart — a professor of biomolecular engineering at the University of California, Santa Cruz — explains, "Insights about how one type of cancer relates to another form of the disease can have real clinical implications."

"In some cases," he continues, "we can borrow clinical practices from better-known diseases and apply them to cancers for which treatment options are less well-defined."

Looking at cancer from the molecular angle also opens up opportunities to explore drugs that are already approved for other diseases that have molecular features that also occur in cancer.

One example of this is the JAK/Stat molecular pathway that is activated in rheumatoid arthritis. The researchers found that this pathway is upregulated in some of the newly defined tumor clusters.

The PanCancer Atlas papers

Each of the three groups of PanCancer Atlas papers is introduced by a flagship, or summary, paper. There are clear links to these and the companion papers on the landing page of the portal.

The first summary paper, which introduces the category titled "cell-of-origin patterns," gives an overview of how researchers used "molecular clustering" to group tumors according to gene expression, chromosome abnormality, and DNA changes.

It suggests that these findings will lead to more specific therapies for different types of cancer.

The second summary paper introduces the "oncogenic processes" category and suggests that the findings will help researchers to decide on priorities about which immunotherapies and other treatments that they should investigate.

As well as giving a broad summary, the paper describes the identification of three critical processes in cancer development: inherited and acquired mutations; how a tumor's genome and epigenome influence gene and protein expression; and interactions between tumor cells and those of the immune system.

The third summary paper, which covers the "signaling pathways" category, sums up the findings concerning alterations to the genome in the signaling pathways that regulate the cell cycle, cell growth, and cell death.

This paper highlights the similarities and differences of these processes for different cancers and suggests that the findings will help to develop new treatments in personalized medicine and combination therapy.

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